Skip to main content
NCBI home page
Thorax logoLink to Thorax
. 1998 Jul;53(7):594–600. doi: 10.1136/thx.53.7.594

Iron metabolism in the lower respiratory tract

F Mateos 1, J Brock 1, J L Perez-Arellano 1
PMCID: PMC1745270  PMID: 9797761

Full Text

The Full Text of this article is available as a PDF (148.8 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alford C. E., King T. E., Jr, Campbell P. A. Role of transferrin, transferrin receptors, and iron in macrophage listericidal activity. J Exp Med. 1991 Aug 1;174(2):459–466. doi: 10.1084/jem.174.2.459. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Andreesen R., Osterholz J., Bodemann H., Bross K. J., Costabel U., Löhr G. W. Expression of transferrin receptors and intracellular ferritin during terminal differentiation of human monocytes. Blut. 1984 Sep;49(3):195–202. doi: 10.1007/BF00319822. [DOI] [PubMed] [Google Scholar]
  3. Andrews S. C., Arosio P., Bottke W., Briat J. F., von Darl M., Harrison P. M., Laulhère J. P., Levi S., Lobreaux S., Yewdall S. J. Structure, function, and evolution of ferritins. J Inorg Biochem. 1992 Aug 15;47(3-4):161–174. doi: 10.1016/0162-0134(92)84062-r. [DOI] [PubMed] [Google Scholar]
  4. Basran G. S., Byrne A. J., Hardy J. G., Richardson M. A. The effect of methylprednisolone on the pulmonary accumulation of transferrin in the adult respiratory distress syndrome. Eur J Respir Dis. 1986 May;68(5):336–341. [PubMed] [Google Scholar]
  5. Baz M. A., Ghio A. J., Roggli V. L., Tapson V. F., Piantadosi C. A. Iron accumulation in lung allografts after transplantation. Chest. 1997 Aug;112(2):435–439. doi: 10.1378/chest.112.2.435. [DOI] [PubMed] [Google Scholar]
  6. Bell D. Y., Haseman J. A., Spock A., McLennan G., Hook G. E. Plasma proteins of the bronchoalveolar surface of the lungs of smokers and nonsmokers. Am Rev Respir Dis. 1981 Jul;124(1):72–79. doi: 10.1164/arrd.1981.124.1.72. [DOI] [PubMed] [Google Scholar]
  7. Bomford A. B., Munro H. N. Transferrin and its receptor: their roles in cell function. Hepatology. 1985 Sep-Oct;5(5):870–875. doi: 10.1002/hep.1840050528. [DOI] [PubMed] [Google Scholar]
  8. Britigan B. E., Hayek M. B., Doebbeling B. N., Fick R. B., Jr Transferrin and lactoferrin undergo proteolytic cleavage in the Pseudomonas aeruginosa-infected lungs of patients with cystic fibrosis. Infect Immun. 1993 Dec;61(12):5049–5055. doi: 10.1128/iai.61.12.5049-5055.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Bullen J. J., Armstrong J. A. The role of lactoferrin in the bactericidal function of polymorphonuclear leucocytes. Immunology. 1979 Apr;36(4):781–791. [PMC free article] [PubMed] [Google Scholar]
  10. Camhi S. L., Alam J., Otterbein L., Sylvester S. L., Choi A. M. Induction of heme oxygenase-1 gene expression by lipopolysaccharide is mediated by AP-1 activation. Am J Respir Cell Mol Biol. 1995 Oct;13(4):387–398. doi: 10.1165/ajrcmb.13.4.7546768. [DOI] [PubMed] [Google Scholar]
  11. Clarkson A. B., Jr, Sarić M., Grady R. W. Deferoxamine and eflornithine (DL-alpha-difluoromethylornithine) in a rat model of Pneumocystis carinii pneumonia. Antimicrob Agents Chemother. 1990 Sep;34(9):1833–1835. doi: 10.1128/aac.34.9.1833. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Corhay J. L., Weber G., Bury T., Mariz S., Roelandts I., Radermecker M. F. Iron content in human alveolar macrophages. Eur Respir J. 1992 Jul;5(7):804–809. [PubMed] [Google Scholar]
  13. Cross C. E., Halliwell B., Borish E. T., Pryor W. A., Ames B. N., Saul R. L., McCord J. M., Harman D. Oxygen radicals and human disease. Ann Intern Med. 1987 Oct;107(4):526–545. doi: 10.7326/0003-4819-107-4-526. [DOI] [PubMed] [Google Scholar]
  14. Custer G., Balcerzak S., Rinehart J. Human macrophage hemoglobin-iron metabolism in vitro. Am J Hematol. 1982 Aug;13(1):23–36. doi: 10.1002/ajh.2830130105. [DOI] [PubMed] [Google Scholar]
  15. Dautry-Varsat A. Receptor-mediated endocytosis: the intracellular journey of transferrin and its receptor. Biochimie. 1986 Mar;68(3):375–381. doi: 10.1016/s0300-9084(86)80004-9. [DOI] [PubMed] [Google Scholar]
  16. De la Cruz J. L., Oteo L. A., López C., Curto L. M., Burgaleta C., Campos A., Sueiro A. Toxic-oil syndrome. Gallium-67 scanning and bronchoalveolar lavage studies in patients with abnormal lung function. Chest. 1985 Sep;88(3):398–402. doi: 10.1378/chest.88.3.398. [DOI] [PubMed] [Google Scholar]
  17. Djeha A., Pérez-Arellano J. L., Brock J. H. Transferrin synthesis by mouse lymph node and peritoneal macrophages: iron content and effect on lymphocyte proliferation. Blood. 1993 Feb 15;81(4):1046–1050. [PubMed] [Google Scholar]
  18. Djeha A., Pérez-Arellano J. L., Hayes S. L., Oria R., Simpson R. J., Raja K. B., Brock J. H. Cytokine-mediated regulation of transferrin synthesis in mouse macrophages and human T lymphocytes. Blood. 1995 Feb 15;85(4):1036–1042. [PubMed] [Google Scholar]
  19. Fang R., Aust A. E. Induction of ferritin synthesis in human lung epithelial cells treated with crocidolite asbestos. Arch Biochem Biophys. 1997 Apr 15;340(2):369–375. doi: 10.1006/abbi.1997.9892. [DOI] [PubMed] [Google Scholar]
  20. Freeman B. A., Crapo J. D. Biology of disease: free radicals and tissue injury. Lab Invest. 1982 Nov;47(5):412–426. [PubMed] [Google Scholar]
  21. Ghio A. J., Pritchard R. J., Dittrich K. L., Samet J. M. Non-heme (Fe3+) in the lung increases with age in both humans and rats. J Lab Clin Med. 1997 Jan;129(1):53–61. doi: 10.1016/s0022-2143(97)90161-x. [DOI] [PubMed] [Google Scholar]
  22. Gonzalez-Villaron L., Pérez-Arellano J. L., de Castro S. Urinary iron excretion in patients with chronic obstructive airways disease (COAD). Ann Clin Biochem. 1995 Jul;32(Pt 4):417–418. doi: 10.1177/000456329503200411. [DOI] [PubMed] [Google Scholar]
  23. Gutteridge J. M., Mumby S., Quinlan G. J., Chung K. F., Evans T. W. Pro-oxidant iron is present in human pulmonary epithelial lining fluid: implications for oxidative stress in the lung. Biochem Biophys Res Commun. 1996 Mar 27;220(3):1024–1027. doi: 10.1006/bbrc.1996.0518. [DOI] [PubMed] [Google Scholar]
  24. Hallman M., Chundu V., Barsotti M., Bry K. Transferrin modifies surfactant responsiveness in acute respiratory failure: role of iron-free transferrin as an antioxidant. Pediatr Pulmonol. 1996 Jul;22(1):14–22. doi: 10.1002/(SICI)1099-0496(199607)22:1<14::AID-PPUL3>3.0.CO;2-K. [DOI] [PubMed] [Google Scholar]
  25. Hallman M., Sarnesto A., Bry K. Interaction of transferrin saturated with iron with lung surfactant in respiratory failure. J Appl Physiol (1985) 1994 Aug;77(2):757–766. doi: 10.1152/jappl.1994.77.2.757. [DOI] [PubMed] [Google Scholar]
  26. Haslam P. L., Parker D. J., Townsend P. J. Increases in HLA-DQ, DP, DR, and transferrin receptors on alveolar macrophages in sarcoidosis and allergic alveolitis compared with fibrosing alveolitis. Chest. 1990 Mar;97(3):651–661. doi: 10.1378/chest.97.3.651. [DOI] [PubMed] [Google Scholar]
  27. Haurani F. I., Meyer A., O'Brien R. Production of transferrin by the macrophage. J Reticuloendothel Soc. 1973 Sep;14(3):309–316. [PubMed] [Google Scholar]
  28. Hay J. G., Haslam P. L., Turner-Warwick M., Laurent G. J. The effects of iron and desferrioxamine on the lung injury induced by intravenous bleomycin and hyperoxia. Free Radic Res Commun. 1987;4(2):109–114. doi: 10.3109/10715768709088095. [DOI] [PubMed] [Google Scholar]
  29. Hirata T., Bitterman P. B., Mornex J. F., Crystal R. G. Expression of the transferrin receptor gene during the process of mononuclear phagocyte maturation. J Immunol. 1986 Feb 15;136(4):1339–1345. [PubMed] [Google Scholar]
  30. Hoidal J. R., Beall G. D., Repine J. E. Production of hydroxyl radical by human alveolar macrophages. Infect Immun. 1979 Dec;26(3):1088–1092. doi: 10.1128/iai.26.3.1088-1092.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Kime R., Gibson A., Yong W., Hider R., Powers H. Chromatographic method for the determination of non-transferrin-bound iron suitable for use on the plasma and bronchoalveolar lavage fluid of preterm babies. Clin Sci (Lond) 1996 Nov;91(5):633–638. doi: 10.1042/cs0910633. [DOI] [PubMed] [Google Scholar]
  32. Kwak E. L., Larochelle D. A., Beaumont C., Torti S. V., Torti F. M. Role for NF-kappa B in the regulation of ferritin H by tumor necrosis factor-alpha. J Biol Chem. 1995 Jun 23;270(25):15285–15293. doi: 10.1074/jbc.270.25.15285. [DOI] [PubMed] [Google Scholar]
  33. LaLonde C., Ikegami K., Demling R. Aerosolized deferoxamine prevents lung and systemic injury caused by smoke inhalation. J Appl Physiol (1985) 1994 Nov;77(5):2057–2064. doi: 10.1152/jappl.1994.77.5.2057. [DOI] [PubMed] [Google Scholar]
  34. Lenz A. G., Costabel U., Maier K. L. Oxidized BAL fluid proteins in patients with interstitial lung diseases. Eur Respir J. 1996 Feb;9(2):307–312. doi: 10.1183/09031936.96.09020307. [DOI] [PubMed] [Google Scholar]
  35. Lum J. B., Infante A. J., Makker D. M., Yang F., Bowman B. H. Transferrin synthesis by inducer T lymphocytes. J Clin Invest. 1986 Mar;77(3):841–849. doi: 10.1172/JCI112381. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. McGowan S. E., Henley S. A. Iron and ferritin contents and distribution in human alveolar macrophages. J Lab Clin Med. 1988 Jun;111(6):611–617. [PubMed] [Google Scholar]
  37. McGowan S. E., Murray J. J., Parrish M. G. Iron binding, internalization, and fate in human alveolar macrophages. J Lab Clin Med. 1986 Dec;108(6):587–595. [PubMed] [Google Scholar]
  38. McGowan S. E., Parenti C. M., Hoidal J. R., Niewoehner D. E. Ascorbic acid content and accumulation by alveolar macrophages from cigarette smokers and nonsmokers. J Lab Clin Med. 1984 Jul;104(1):127–134. [PubMed] [Google Scholar]
  39. Miller R. A., Rasmussen G. T., Cox C. D., Britigan B. E. Protease cleavage of iron-transferrin augments pyocyanin-mediated endothelial cell injury via promotion of hydroxyl radical formation. Infect Immun. 1996 Jan;64(1):182–188. doi: 10.1128/iai.64.1.182-188.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Momotani E., Furugouri K., Obara Y., Miyata Y., Ishikawa Y., Yoshino T. Immunohistochemical distribution of ferritin, lactoferrin, and transferrin in granulomas of bovine paratuberculosis. Infect Immun. 1986 May;52(2):623–627. doi: 10.1128/iai.52.2.623-627.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Nelson M. E., O'Brien-Ladner A. R., Wesselius L. J. Regional variation in iron and iron-binding proteins within the lungs of smokers. Am J Respir Crit Care Med. 1996 Apr;153(4 Pt 1):1353–1358. doi: 10.1164/ajrccm.153.4.8616566. [DOI] [PubMed] [Google Scholar]
  42. Olakanmi O., McGowan S. E., Hayek M. B., Britigan B. E. Iron sequestration by macrophages decreases the potential for extracellular hydroxyl radical formation. J Clin Invest. 1993 Mar;91(3):889–899. doi: 10.1172/JCI116310. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Otterbein L., Sylvester S. L., Choi A. M. Hemoglobin provides protection against lethal endotoxemia in rats: the role of heme oxygenase-1. Am J Respir Cell Mol Biol. 1995 Nov;13(5):595–601. doi: 10.1165/ajrcmb.13.5.7576696. [DOI] [PubMed] [Google Scholar]
  44. Pacht E. R., Davis W. B. Role of transferrin and ceruloplasmin in antioxidant activity of lung epithelial lining fluid. J Appl Physiol (1985) 1988 May;64(5):2092–2099. doi: 10.1152/jappl.1988.64.5.2092. [DOI] [PubMed] [Google Scholar]
  45. Pantopoulos K., Weiss G., Hentze M. W. Nitric oxide and oxidative stress (H2O2) control mammalian iron metabolism by different pathways. Mol Cell Biol. 1996 Jul;16(7):3781–3788. doi: 10.1128/mcb.16.7.3781. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Popp W., Herkner K., Böck A., Rauscher H., Wanke T., Ritschka L., Zwick H. Influences of the cellular and humoral immune system in bronchoalveolar lavage on lung function in pulmonary sarcoidosis. Respiration. 1992;59(2):89–93. doi: 10.1159/000196033. [DOI] [PubMed] [Google Scholar]
  47. Pérez-Arellano J. L., Losa-García J. E., Orfao-Matos A., González M., de la Cruz J. L., Jiménez A., de Castro S. Comparison of two techniques (flow cytometry and alkaline immunophosphatase) in the evaluation of alveolar macrophage immunophenotype. Diagn Cytopathol. 1993;9(3):259–265. doi: 10.1002/dc.2840090304. [DOI] [PubMed] [Google Scholar]
  48. Quan S. G., Golde D. W. Identification and localization of toxic elements in normal human lung macrophages. Proc Soc Exp Biol Med. 1981 Jun;167(2):175–181. doi: 10.3181/00379727-167-41145. [DOI] [PubMed] [Google Scholar]
  49. Raja K. B., Pippard M. J., Simpson R. J., Peters T. J. Relationship between erythropoiesis and the enhanced intestinal uptake of ferric iron in hypoxia in the mouse. Br J Haematol. 1986 Nov;64(3):587–593. doi: 10.1111/j.1365-2141.1986.tb02214.x. [DOI] [PubMed] [Google Scholar]
  50. Rich E. A. Iron metabolism by smokers' alveolar macrophages: protective or problematic in the lung? J Lab Clin Med. 1988 Jun;111(6):598–599. [PubMed] [Google Scholar]
  51. Ryan T. P., Krzesicki R. F., Blakeman D. P., Chin J. E., Griffin R. L., Richards I. M., Aust S. D., Petry T. W. Pulmonary ferritin: differential effects of hyperoxic lung injury on subunit mRNA levels. Free Radic Biol Med. 1997;22(5):901–908. doi: 10.1016/s0891-5849(96)00483-2. [DOI] [PubMed] [Google Scholar]
  52. Smith K. R., Aust A. E. Mobilization of iron from urban particulates leads to generation of reactive oxygen species in vitro and induction of ferritin synthesis in human lung epithelial cells. Chem Res Toxicol. 1997 Jul;10(7):828–834. doi: 10.1021/tx960164m. [DOI] [PubMed] [Google Scholar]
  53. Smith R. L., Berkowitz K. A., Lewis M. L. Pulmonary disposition of gallium-67 in patients with Pneumocystis pneumonia: an analysis using bronchoalveolar lavage. J Nucl Med. 1992 Apr;33(4):512–515. [PubMed] [Google Scholar]
  54. Stites S. W., Nelson M. E., Wesselius L. J. Transferrin concentrations in serum and lower respiratory tract fluid of mechanically ventilated patients with COPD or ARDS. Chest. 1995 Jun;107(6):1681–1685. doi: 10.1378/chest.107.6.1681. [DOI] [PubMed] [Google Scholar]
  55. Testa U., Petrini M., Quaranta M. T., Pelosi-Testa E., Mastroberardino G., Camagna A., Boccoli G., Sargiacomo M., Isacchi G., Cozzi A. Iron up-modulates the expression of transferrin receptors during monocyte-macrophage maturation. J Biol Chem. 1989 Aug 5;264(22):13181–13187. [PubMed] [Google Scholar]
  56. Thompson A. B., Bohling T., Heires A., Linder J., Rennard S. I. Lower respiratory tract iron burden is increased in association with cigarette smoking. J Lab Clin Med. 1991 Jun;117(6):493–499. [PubMed] [Google Scholar]
  57. Thompson A. B., Bohling T., Payvandi F., Rennard S. I. Lower respiratory tract lactoferrin and lysozyme arise primarily in the airways and are elevated in association with chronic bronchitis. J Lab Clin Med. 1990 Feb;115(2):148–158. [PubMed] [Google Scholar]
  58. Thompson A. B., Mueller M. B., Heires A. J., Bohling T. L., Daughton D., Yancey S. W., Sykes R. S., Rennard S. I. Aerosolized beclomethasone in chronic bronchitis. Improved pulmonary function and diminished airway inflammation. Am Rev Respir Dis. 1992 Aug;146(2):389–395. doi: 10.1164/ajrccm/146.2.389. [DOI] [PubMed] [Google Scholar]
  59. Vostrejs M., Moran P. L., Seligman P. A. Transferrin synthesis by small cell lung cancer cells acts as an autocrine regulator of cellular proliferation. J Clin Invest. 1988 Jul;82(1):331–339. doi: 10.1172/JCI113591. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Wesselius L. J., Flowers C. H., Skikne B. S. Alveolar macrophage content of isoferritins and transferrin. Comparison of nonsmokers and smokers with and without chronic airflow obstruction. Am Rev Respir Dis. 1992 Feb;145(2 Pt 1):311–316. doi: 10.1164/ajrccm/145.2_Pt_1.311. [DOI] [PubMed] [Google Scholar]
  61. Wesselius L. J., Nelson M. E., Skikne B. S. Increased release of ferritin and iron by iron-loaded alveolar macrophages in cigarette smokers. Am J Respir Crit Care Med. 1994 Sep;150(3):690–695. doi: 10.1164/ajrccm.150.3.8087339. [DOI] [PubMed] [Google Scholar]
  62. Wesselius L. J., Smirnov I. M., Nelson M. E., O'Brien-Ladner A. R., Flowers C. H., Skikne B. S. Alveolar macrophages accumulate iron and ferritin after in vivo exposure to iron or tungsten dusts. J Lab Clin Med. 1996 Apr;127(4):401–409. doi: 10.1016/s0022-2143(96)90188-2. [DOI] [PubMed] [Google Scholar]
  63. Wyllie J. C. Transferrin uptake by rabbit alveolar macrophages in vitro. Br J Haematol. 1977 Sep;37(1):17–24. [PubMed] [Google Scholar]

Articles from Thorax are provided here courtesy of BMJ Publishing Group

RESOURCES